HHV-6B associated with severe GVHD and may explain “fever of unknown origin” in 30% of pediatric stem cell transplant patients

A team from the University of Leiden, Netherlands, reports that HHV-6 may be the cause of “fever of unknown origin” in 30% of stem cell transplant (SCT) patients. By the third week after SCT, 70% of HHV-6 positive patients had a skin rash, compared to 39% of HHV-6 negative patients (P=0.01).

HHV-6 has also been identified as a major cause of ‘fever of unknown origin’ in pediatric patients admitted to the emergency rooms with fever. The virus was found in the plasma of 15% of febrile pediatric patients compared to 0% of afebrile controls (Colvin 2012).

The study, published this month in Pediatric Infectious Disease, reports overall HHV-6 reactivation in 48% of 106 patients, with a median onset of 20 days post-transplant, coinciding with monocyte engraftment and the appearance of lymphocytes and monocytes in the peripheral blood.

HHV-6 viremia was also highly associated with increased severity of aGVHD, as progression to grade 2-4 GVHD occurred almost exclusively in patients with HHV-6 reactivation (P=.006). HHV-6 was found to be the most common infection in patients who progressed to severe GVHD, with HHV-6 preceding aGVHD in 100% of cases. Patients progressing to aGVHD did not have high viral loads; over half had viral loads of less than 1000 copies/ mL, and none had infections lasting longer than 14 days.

Many past studies have concluded that HHV-6 may play a crucial role in the pathogenesis of acute GVHD including several this year (Gotoh 2014, Akoi 2015). Other studies have also suggested a role for HHV-6 in graft failure (Le Bourgeois 2014),

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ABOUT THE HHV-6 FOUNDATION

The HHV-6 Foundation in a non-profit entity founded to encourage scientific exchange between investigators and to provide pilot grants for promising scientific and clinical research on the under- appreciated viruses HHV-6A and HHV-6B.

The Foundation sponsors international conferences and supports scientists and clinicians seeking to clarify the role of the two HHV-6 viruses in disease. Since HHV-6A and HHV-6B can smolder in the brain and other organs without circulating in the peripheral blood or plasma, identifying chronic infection is a challenge.